49-1449140"0491‘0%Gor

Troph opathic Diseases or SystemicNutritional Disturbances as

Reflected in the Mouth

By Grant H. Laing, M.S., M.D.

Chicago, Illinois

Reprinted fromThe Fortnightly Review of the Chicago Dental Society

October 1, 1949

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Dr. Laing

Trophopathic Diseases or Systemic Nutritional

Disturbances as Reflected in the Mouth*

By Grant H. Laing, M.S.., M.D.,t Chicago, Illinois

[EDITOR'S NOTE: At first glancethis article may not attract the reader'sinterest; the subject matter appears tobe completely foreign to dentistry. How-ever, we assure our readers that if theywill but read it, they will be fascinatedby it.]

triophopathic diseases is a termwhich I suggest as a classificationof a group of systemic clinical en-

tities due primarily to nutritional dis-turbances, which you, as dentists, seereflected in the oral cavity.

I believe there is a common denomina-tor as an etiologic basis in pellagra, sprue,pernicious anemia, and certain degenera-tive diseases of the central nervous sys-tem, even though, pathologically, differ-ent anatomical systems are predominantlyinvolved. This common denominator isfundamentally a disturbance of nutritionbased on a failure of certain enzyme sys-tems to function normally. The purposeof this paper is to attempt to correlatesome of these facts in the light of ourpresent knowledge.

• Presented at the Midwinter Meeting of theChicago Dental Society, February, 1 949.

tSenior Attending Physician, St. Luke's Hos-pital, Chicago; Assistant Professor of Medicine,Northwestern University Medical School.

The concept of the electrical constitu-tion of matter ishardly more thanthree decades old,but the resultingimpact on man'sthinking has beenstaggering to theimagination. Whenanyone mentions theatomic bomb or thesplitting of theatom, most of usvisualize first an ap-palling loss of lifeas part of a war tragedy. On secondthought, our minds turn to some peace-ful application of atomic power, suchas, the driving of a large ship acrossthe Atlantic Ocean by means of a poundof atomic fuel. Since it is natural for usto think in medical terms, the third ideathat might occur to us is the use of radio-active isotopes in tracer studies of themetabolism of the body, and the betterutilization of radioactive substances astools in modern medical therapy.

ATOMIC AND NUCLEAR FORCES

This morning I should like to discusswith you an atomic relationship quitedifferent from those already mentioned;namely, the concept that atomic and

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nuclear forces dominate all the metabolicprocesses of the human body. Also, thatonly as we understand the fundamentalsof atomic structure, how the electrons,protons and neutrons control the rela-tionships of atoms, how the atoms andtheir charges determine the activity ofmolecules, and how the molecules in turndirect the course of all systemic reactions,can we intelligently diagnose human dis-eases and plan logically for adequateremedy. In other words, and in the lastanalysis, all the millions of changes whichare constantly in progress in every humanorganism are either normal or abnormal,depending upon the balancing of the posi-tive and negative electrical forces of thereacting components. In fact, all the ac-tivities of the body, mental and physical,may be looked upon as being activatedby differences in electrical potential, be-tween the atoms and the molecules, insideand outside the billions of cells of whichour bodies are made. Of course, the ag-gregates of molecules are ordinarily called"chemical compounds," and it is of thesesimplified entities that we usually thinkwhen we discuss body reactions. We say,for instance, that magnesium combineswith chlorine to form magnesium chlor-ide. What we generally fail to reveal isthat magnesium chloride does not act inthe body as such, in the bound state aspart of a salt. Only in the dissociatedform, wherein aqueous solution magne-sium acts independently of chlorine, isthe body benefited or harmed by the in-take of this salt. Here it is important tonote that this is true also of the activityof all other salts, as well as of combina-tions of other chemical groups to formsubstances that are known as enzymes,which are organic catalysts produced byliving organisms.

In fact, it is this particular form ofcombination—called the enzyme form—which controls the activities of all othersubstances and reactions in the body. Itis this type of product, made up as it isin great variety of positive and negativeradicals, especially balanced for specificpurposes, which directs the course of themetabolic processes of the human organ-ism. Whatever function of the body you

may consider, whether it is tooth growth,gastric digestion, muscular movement,mental concentration, or the mere processof blushing, many enzymes play a role intheir initiation and control. They are theprime movers of all body activity; thecatalyzers, the directors, the governors,the controls.

ENZYMES

Essentially, enzymes may be viewed asa three-way combination of a metal, aspecific protein complex, and one ormore vitamins.' Until recently it wasthought that only one vitamin was to befound in any one enzyme, but with thediscovery that folic acid is a vitamincomposed in part of another vitaminknown as para-amino-benzoic acid, it isconceived that two (or even more) vita-mins may combine to form one of thethree links in the enzyme chain. The na-ture of the activities of the enzymes de-pends obviously upon the kinds of metals,vitamins and proteins involved. It islogical when any one of these three com-ponents is altered, either as to type orquantity, that the resulting activity maybe changed in character and degree.These enzymes are the tools which thebody uses to direct its mental and physicalactivities. They are the things which firstget out of gear when the processes of thebody become abnormal. The preventionor remedy of disease must, therefore,come through proper use or manipula-tion of these systems. We know that wecan repress some of them by drug admin-istration, but what we have yet to learnis still more important; namely, how wecan stimulate the activity of those thatare functioning subnormally, or perhapshardly at all, even though working in theproper direction.

As dentists, you may logically ask whatthese enzymes have to do with the prob-lems associated with the diagnosis andtreatment of abnormalities of the oralcavity. The answer is that many enzymesystems are involved in the growth of thetooth, its normal nutrition, and its repairprocesses. Among these I will mentiononly one; namely, alkaline phosphatase.

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This enzyme is activated by magnesiumand has to do with the deposition of cal-cium and phosphorus in tooth structuresand bone in general. It is also concernedin the metabolism of phospholipids of thenervous system, carbohydrates, and neu-cleotides.

As for the saliva, the principal enzymein the human saliva is ptyalin, which isan amylase. There are also present urease,protease, lipase, maltase, and catalase.There is some evidence that urease aidsin protecting tooth structure from cariesdecomposition by forming ammoniafrom the urea present in the saliva, thusproducing alkalinity which tends to offsetthe damaging effects of the acid-produc-ing bacteria.

VITAMIN C DEFICIENCY

You are all familiar with gingivitis andthe relationship of Vitamin C deficiencyas one of the factors producing patholog-ical changes in the endothelial walls ofthe capillaries, because of a reduction inthe amount of intercellular substance.When this deficiency is marked, the gin-giva are swollen, spongy and hemor-rhagic; bone is absorbed in the alveolarprocesses, and the teeth become loosened.All fibrous tissue in the body is involvedin the extreme condition of scurvy, butthe dentin, cartilage, bone and vascularendothelium are especially involved.

The tongue is an organ which mayreflect in vivid fashion many pathologicalstates resulting from the imbalance ofvarious enzymatic systems. Very strikingamong these are the disease entitiesknown as sprue, pellagra and perniciousanemia. For example, Bicknell and Pres-cott2 say:

"These are three separate disease en-tities, but there is good reason for believ-ing that they are allied nutritional dis-eases. There are many symptoms com-mon to all of them—gastro-intestinalsymptoms, neurological manifestationsand a macrocytic anemia. A patient withachlorhydria, stomatitis, glossitis, diar-rhea, mental depression, involvement ofthe lateral and posterior columns of the

spinal cord, and severe anemia, but nocutaneous lesions, may be suffering fromany one of them. If, in addition, there isa characteristic symmetrical, bilateral, ex-foliative dermatitis of the hands and feet,a diagnosis of pellagra may be made; ifthe anemia responds to injections of liverand returns on withdrawing the latter,pernicious anemia is diagnosed; while thepassage of large, fatty, fermenting andpasty stools confirms the diagnosis ofsprue."

These authors have very aptly ex-pressed the close relationship of thesediseases, but I should like to emphasizefurther some of the various aspects. Inany one of the three, we may have ahighly variable picture that ranges fromthe symptoms and signs of anemia on theone hand, to those of marked involve-ment of the nervous system on the other.As, for example, in pernicious anemia,when the neurological symptoms aremarked, the disease is classified as sub-acute combined degeneration of the cord.However, if the anemia picture is pre-dominant, then the patient is classifiedas a macrocytic anemic and treated assuch. The tingling and numbness, whichare often present, are due to peripheralneuritis and may occur many months be-fore the hematologic findings are evident.

PELLAGRA

The classical picture of pellagra astaught with the three "Ds"—diarrhea,dementia and dermatitis—is rather mis-leading. Clinically, the triad is seldomseen except in advanced cases. The earlysymptoms are bizarre and ill defined.There may be abdominal pain, muscularweakness, and nervous manifestations,ranging from numbness of the extremitiesto morbid features and mental confusion,so that we may have peripheral neuritis,encephalopathy, and subacute combineddegeneration of the cord occurring in anycombination—together or singly—in apatient. The tongue early in the diseaseis red and swollen at the tip and lateralmargins, and there is often a burningsensation which may extend down into

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Mark AndersonHighlight

Mark AndersonHighlight

Mark AndersonHighlight

the esophagus and stomach. In my expe-rience, glossitis and the neurologicalsymptoms are the commonest findings,and they occur in individuals with badfood habits which may or may not beassociated with alcoholism. They are alsofound in the so-called "conditioned pel-lagra," secondary to organic disease, espe-cially of the gastro-intestinal tract. Thesymptomatology3 is most marked in thespring and summer months, so in theendemic cases it is definitely seasonal inits incidence.

The consensus in recent years has beenthat tropical sprue, non-tropical sprueand celiac disease are fundamentally thesame condition. But here again there maybe involvement of several systems. Ifcertain nutritional defects are dominant,the disease is classified as macrocytic hy-perchromic anemia. Yet, as stated above,one of the major complaints is diarrhea.Glossitis may precede such diarrhea bymany months, the tongue and mouth be-come sensitive, and a stomatitis develops.Later it becomes beefy red with atrophyof the filiform papillae, and finally, inlong-continued cases, smooth and shiny.Paresthesias (or numbness) of the handsand feet, denoting peripheral neuritis, arecommon, but the subacute combined de-generation of the spinal cord is rare ascompared with its manifestations in per-nicious anemia. However, depression,memory loss, irritability and emotionalinstability may occur. The diet in theseindividuals has been excessive in carbo-hydrates and low in proteins, as in pel-agra.

DEMYELINATION

The neurological findings in the nutri-tional diseases of sprue, pernicious ane-mia and pellagra are due, as you play beanticipating, to the partial loss of thenerve coverings or sheaths—a processcalled "demyelination." Such demyelina-tion may occur in slight or marked degreein the peripheral nerves, or in the spinalcord, or in the brain. The myelin sheath'of the nerve fibers is a semi-fluid, fattysubstance, almost white in color. One ofits functions is to protect the nerves

against irritation or damage. Another, aswill be noted later, is to aid in the trans-mission of nerve impulses. This sheath,which is part of the neuron (a structuralunit of the nervous system), is ectodermalin origin, and is the most vulnerable ofall nerve cells in the central nervous sys-tem, according to Cobb. 5 It is said to bedamaged before the axon in such diseasesas measles, chicken pox and avitaminosis.A general rule is that the larger, moreswiftly conducting axons—which arethose with the highest specialization offunction—have the thickest myelinsheaths. Incidentally, thiamine is essen-tial in maintaining the energy supply ofthe myelin sheath, and in metabolizinggalactose with the formation of galacto-lipids which constitute about one-third ofthe lipids of the white matter of braintissue. Thiamine is the coenzyme of theenzyme carboxylase, which catalyzes oneof the steps in the oxidative metabolismof carbohydrates, such as glucose. Dis-turbance of this mechanism at this stageleads to an accumulation of pyruvic acidwhich aggravates the breaking down ofthe myelin sheath.

E. Weston Hurst,' using repeated smalldoses of carbon monoxide (CO), potas-sium cyanide (KCN) or sodium azide(NaN,), produced experimental demye-lination in animals. Similar changes fol-lowed the administration of barbituratesto monkeys. Larger doses of KCN pro-duced in monkeys a necrosis of the whitematter which occurred suddenly and si-multaneously over considerable areas ofthe cerebral hemispheres—a conditionnot unlike the lesions of Schilder's en-cephalitis in man and the monkey. Ac-cording to Hurst, demyelination is abiochemical process involving the metab-olism of some enzyme system which isessential to myelin nutrition.

Another observation of great impor-tance is the possible correlation of copperdeficiency in soils with myelin degenera-tion in sheep and in their offspring. Thedisease is known as "swayback," or "pin-ing," or as "enzootic ataxia." Its symp-toms are similar to those of Schilder'sdisease in man.'

Follis' presents a very intriguing hypo-

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thesis, based on experimental work withswine, in which he states that pyridoxineis intimately connected with the metabol-ism of myelin, and that pantothenic acidaffects the integrity of the cell body itself.He further states that in myelinoclasticdiseases, such as multiple sclerosis, themyelin sheath is primarily affected, whilein polioclastic diseases, such as epidemicencephalitis, the cell body is first injuredand myelin degeneration follows.

RELATED DISEASES

Three disease entities have been re-viewed in considerable detail for the pur-pose of demonstrating the fact to youthat they all have a common denomina-tor as far as the nervous system is con-cerned; namely, demyelination. Theyshare this pathological process with sev-eral other diseases which, on first thought,seem not to be at all related. Among theseare the following: (t) multiple sclerosis,(2) amyotrophic lateral sclerosis, (3)Friedreich's disease, (4) Schilder's dis-ease, (5) Devic's disease, and (6) cer-tain types of neuritis.

Reference will be made to multiplesclerosis as an example. It is often called"disseminated sclerosis," and is at presentone of the commonest chronic diseases ofthe central nervous system. It appears tobe on the increase in the United States,but the incidence here is much less thanin certain parts of Europe. The cause ofthe disease is unknown, and the oldertheories have been disproved. Among thenumerous new theories that have beenadvanced is that of Morrison,10 who hassucceeded experimentally in producinglesions which resemble those of multiplesclerosis by injection of autoantigens.This suggests a possible relationship withsensitization."

But, before further attempting to ex-plain a possible correlation of these re-lated diseases to specific causative fac-tors, I feel that I must emphasize anothercommon denominator influence; namely,that nervous tissue exhibits a markedpreference for carbohydrates as a sourceof metabolic energy. In other words, glu-

cose and its equivalents are constantlyutilized in the maintenance of nerve formand stability, as well as in the energizingof nerve activities. Obviously, when andif there is any interference with the proc-esses of conversion of carbohydrates totheir ultimate breakdown products ofcarbon dioxide and water, there is aptto be nerve irritation, or some degree ofdysfunction.

However, this is a very simple state-ment of a very complex picture. As Dr.Carl F. Cori" explains, glucose is con-verted by step-wise addition of phos-phates to simple organic acids, such aspyruvic, lactic, acetic and carbonic, andthere are eleven distinct steps in thetransition pathway. Each of these stepsliberates an additional amount of energyand each is activated by a different en-zyme. These added phosphates, throughenzyme systems of their own, act as en-ergy carriers by operating what might becalled a "shuttle service" between theend products of one reaction and thestarting components of the next.

STRATEGIC FACTORS

And this again brings us face to facewith a concept that enzyme systems arestrategic factors in all these problems.Whatever aids the functioning of the en-zymes involved in the nutrition andhealth of the body's nerves, muscles, andother tissues, helps to prevent or to rem-edy these myelin deficiency diseases. Con-versely, whatever damages these enzymesystems becomes a possible causative fac-tor in the precipitation of these bafflingailments. It is important, therefore, tonote some of the substances which com-monly inactivate such enzyme systems.Some examples are as follows:

t. Bacteriotoxins—Pneumonia, Scar-let fever, Diphtheria, Erysipelas.

2. Viruses — Poliomyelitis, Chickenpox, Measles, Herpes Zoster.

3. Chemicals and Drugs—Arsenic,Alcohol, Barbiturates, Carbon monoxide,Cyanides, Gold, Lead, Mercury. The listof these dangerous substances is growing

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because of the rapid development of ourchemical industries.

4. Mineral Deficiencies—Iodine defi-ciency, as commonly found through theso-called goiter belt of the United States,is a typical example. Similar deficienciesare those of manganese, cobalt, and mag-nesium in the North Central States.

5. Mineral Excesses—Too much po-tassium, iron and fluorine are commonexamples.

6. Vitamin and Essential Amino AcidDeficiencies—As dentists, you can appre-ciate the fact that any one or several vita-mins can be deficient under certain con-ditions, which is also true of the essentialamino adds. An interesting illustration ofthe profound effect of system involvementon oral manifestations is the transverseridging of the teeth. It may be found inseveral acute infections, like scarlet fever,in a poorly controlled diabetic child, ora rachitic child. The explanation for itis a marked disturbance in metabolism,resulting in a temporary interferencewith tooth growth.

Further experimental work in animalswhich is highly significant is that ofWarkany," who states:

"There exists a widespread beliefamong the laymen, as well as amongphysicians, that systemic and multiplecongenital malformations are always theresult of changes in the "germ plasm,"that is, genetically determined and hered-itary. This belief is not correct; in fact,it has been shown repeatedly that devel-opmental processes can be altered byenvironmental disturbances in the sameway as by abnormal genes. It will be ofgreat interest to the geneticist that typesof congenital malformations, which aresometimes genetically determined, suchas microthalmos, cleft palate, brachygna-thia, and the like, can be produced in theoffspring by maternal deficiencies of welldefined chemical substances like VitaminA or riboflavin. Since it has been sug-gested that genes act as enzymes, it maybe worth while to point out that ribofla-vin is known to be an essential constituent

of a number of enzyme systems whichperform specific functions."

7. Vitamin Excesses—Syndenstricker"has reported that when niacin was givenalone to patients with pellagra, cer-tain signs of their disease, presumably dueto deficiency in other factors, are intensi-fied. Hopkins" mentioned that excess ofcod-liver oil was injurious to rats. It haslong been known that rich sources ofVitamins A and D may be toxic whengiven in great excess.

8. Antivitamins—This is a subjectwhich has received but little attention,yet is of vast importance. I can do nobetter than to quote Wooley throughGreen" on this fascinating subject.

"Wooley" has , pioneered in providinga framework for a rational pharmacologybased on the antivitamin concept. Heshowed that certain antivitamins canproduce a state of avitaminosis, in somecases in a matter of hours, merely by dis-placing the vitamins competitively fromtheir catalytic complexes. Since profoundpharmacological effects attend the syn-drome of avitaminosis, antivitamins haveto be regarded as potential pharmacolog-ical agents. Thus, pyrithiamine rapidlyinduces the disorders of the central nerv-ous system which are characteristic ofthiamine deficiency. The lesion is, ofcourse, righted at once by addition oflarge enough amounts of thiamine. Sincethe quantitative importance of the cata-lytic reaction in which vitamins partici-pate varies, depending upon the organor part of organ, it does not follow thatall antivitamins will exhibit similarpharmocological effects. On the contrary,it would appear that each antivitaminwould selectively poison only a particularportion of the nervous system, as wellas only particular organs. A completeseries of antivitamins should provide awide range of specific pharmacologicalagents, all of which are reversible byaddition of the vitamins which they imi-tate. The beginnings in this new field ofexploration are still modest, but the hori-zons seem immense."

It is significant that the action of sul-

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fonamide is through its interference withthe growth of bacteria by its competitivedisplacements of para-aminobenzoic acidin the nutrient medium.

MINERAL ELEMENTS

In what has gone before I have men-tioned a number of mineral elements,but have not stressed them particularly.Now, I wish to remind you that in justthe few enzyme systems involved in nerve,brain and muscle tissue, at least the fol-lowing mineral elements participate: sul-phur, magnesium, manganese, calcium,phosphorus, zinc, cobalt, iron, and cop-per. I am quite sure that there are others,but this is enough to support the conceptthat the diseases which involve primarilythe bone marrow, the blood stream, thelungs, the stomach, the teeth, the muscles,and nerves—and, secondarily, all the or-gans and parts of the body—are inti-mately related to the problem of themineralization of the nation's soils.

If these and the other minerals re-quired by our bodies are plentifully sup-plied to the plants on which we, or ourfood-supply animals live, then we can befairly sure that our own foods will befully enriched and adequate. But, if ourfarm soils are not thus adequately miner-alized, it is equally certain that we as apeople are going to suffer increasinglyfrom the many diseases that are caused

directly and indirectly by food-factordeficiencies.

According to a well known authority,Dr. Jacob G. Lipman" of the New JerseyAgricultural Experiment Station, the an-nual loss of mineral elements from theagricultural soils of the nation is littleshort of alarming. For instance, in oneyear for which suitable figures were as-sembled, the gross losses, fertilizer gains,and net losses of minerals were for arablesoils and pastures as given in this chart.The "losses" include removal of mineralsby cropping and by erosion through windand water. The "gains" comprise addi-tions of fertilizers, manures, bedding,rainfall, irrigation, seeds and fixed nitro-gen.

Probably no worth-while estimate is tobe found of the losses from soils of all theother minerals which are utilized by plantand animal life, but it is only reasonableto assume that the depletion of otherminerals is very much in proportion tothose enumerated in the chart. It is,therefore, equally serious from the stand-points both of crop quantity and foodquality.

Obviously, excessive growth of a plantis not a measure of plant health, or acriterion of its nutritive value for humanbeings, any more than is excessive size ofthe body a measure of a person's healthstatus. Nitrogen, potash, phosphates andlime—which constitute the principal

Annual Balance of Plant Nutrients in Soils of the United States, soo

TONS

LOSSES(Harvested Crops,Grazing, Erosion,

Leaching)

ADDITIONS(Fertilizers and Liming

Materials, Manures andBedding, Rainfall, Irri-gation Waters, Seeds

Nitrogen Fixed)

NET ANNUALLOSS

NITROGEN 22,899,046 16,253,862 6,645,184PHOSPHORUS 4,221,302 1,447,835 2,773,467POTASSIUM 50,108,560 5,151,076 44,957,484CALCIUM 68,185,730 12,561,673 55,624,057MAGNESIUM 24,557,881 4,040,813 20,517,068SULPHUR 12,043,901 9,029,690 3,014,221

(All figures subject to change and correction.)

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mineral elements in commercial fertilizer—can produce increasing crop yieldswhen supplied liberally to run-down soils.But these do not assure crops of greatestnutritive value. In fact, the opposite re-sult may often be obtained. For an excessof lime will render iron, manganese,boron and other essential elements rela-tively unavailable to the plant.

IMBALANCE OF MINERALS

This explains to some extent why animbalance of minerals increases the sus-ceptibility of plants—both fruits and veg-etables—to blight and to rotting, and alsowhy it is important for humans to useas foods only those plants (or the animalsliving on such plants) that are knownto be internally sound and healthy, ratherthan those that are good merely in out-ward appearance. For it is not only thepick-up of minerals obtained from wellnourished plants that counts—it is stillmore important that such plants containthe complex organic substances whichplants synthesize through the mediationof the complete soil mineral assortment.This further explains also how the min-eral composition of the soil influences thevitamin content of the plant. For in-stance, boron in the soil increases theVitamin A content of apples, and man-

ganese enhances the vitamin content oftomatoes, strawberries, and other fruits."Mottle leaf" of citrus, and "rosette" offruit trees are common diseases knownto be due to a deficiency of zinc. Men-tioning only a few of the minerals whichplay a strategic role in animal nutrition,I remind you that copper, as has longbeen known, is an important factor in theformation of hemoglobin. It also is acomponent of the ascorbic oxidase en-zyme, and of the enzyme tyrosinase,which has to do with the metabolism oftyrosine, one of the vital amino acids. Asin plants, however, so in animals, thereis such a thing as an excess of copper. Itcan become a body poison.

Cobalt, too, is related to hemoglobinsynthesis, and its biological importance isrevealed by the fact that it is a compo-nent of the recently discovered VitaminB . 12. This vitamin is being heralded as ofvalue in the treatment of the neurologicand hematologic phases of pernicious andother types of rnacrocytic anemias. Whileresults are yet to be proved, it is signifi-cant that a metal such as cobalt is appar-ently a catalyzer of this vitamin activity.A material excess of cobalt produces anabnormal increase in red blood cells, ora condition known as polycythemia. Themost recently discovered member of theVitamin B complex is B 14. It is possible

Amino Acid Content of Alfalfa Hay According to Soil Treatments withTrace Elements

(PERCENTAGE OP DRY LEAVES)

Plot No. 1. 2. 3. 4.

Calcium & Calcium & Calcium &Treatment Calcium Manganese Boron Mixture*

Valine 2.19 2.40 2.13 2.59Lucine 4.37 4.89 5.55 5.24Arginine 0.380 0.434 0.418 0.415Histidine 0.654 0.807 0.726 0.835Threonine 0.862 0.954 1.071 1.014Tryptophane 0.546 0.640 0.856 0.6701.ycine 1.57 2.12 2.13 1.871 soleuci ne 2.64 3.63 4.09 3.44Methionine 0.100 0.242 0.173 0.229

• Mixture of cobalt, copper, zinc, manganese, and bosun.

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that it will prove to have a bearing on theformation of some part of the hemoglobinmolecule."

ZINC

Zinc is another mineral element whichplays a role in many metabolic processesof the human body. It is associated withthe production of insulin, with the releaseof carbon dioxide from the blood into thelung spaces, and possibly with the forma-tion of gastric juice by the stomachmucosa. Strange as it may seem, the con-centration of zinc in the dentin is manytimes greater than in the blood stream,yet apparently none of it is found in thetooth enamel As a component of theenzyme, carbonic anhydrase, zinc is con-cerned with the speed of impulse trans-mission in the nervous system.

As for phosphorus and potassium, allplants need them for growth and Lothare required in liberal quantities by ani-mals and man However, an excess ofpotassium can be toxic to man, for insuch quantities it suppresses nerve im-pulse transmission and causes paralysis.Likewise, in the soil, an excess of potas-sium interferes with proper plant growthand retards the synthesis of some of theB complex vitamins. Also a lack of phos-phate reduces the synthesis of riboflavinby plants and in animals has severaldeleterious effects, e.g., the excessive ex-cretion of calcium. As one authority, Dr.H. H. Mitcl2e112°, University of Illinois,says : "Regardless of huge stores of phos-phorus in the skeleton, the animal liveson a hand to mouth phosphorus supplyfor anabolic uses."

Now considering that an importantfactor in the enzyme systems of the bodyis the protein content, it is well to noteexperiments by Sheldon, Blue and Al-brecht," Missouri Agriculture Station,who, along with other prominent re-searchers, have shown conclusively thateven minor deficiencies of the so-calledtrace minerals in soil greatly alter thecharacter of the protein content of ani-mal and human foods. For example, thischart shows that as we vary the calciumcontent of soils, the ratios of the amino

acids of hay, alfalfa, and lespedeza arematerially altered. The same is obtainedby changing the soil content of copper,boron, cobalt, manganese, and zinc.These are only a few examples of thedamaging effects resulting from soil defi-ciencies of these items. In other words,it is easy enough to understand from thesefigures that the composition of the hayor wheat or corn, or of any other cropgrown in a particular part of the UnitedStates 5o or zoo years ago was quitedifferent from the composition of thesame plants grown in the same soil today.

It thus becomes apparent that there isa balance in nature which cannot safelybe ignored, and this applies first to soil,then to plants, animals, and man,—sinceman acquires all the elements that consti-tute his makeup from these sources.

SUMMARY AND CONCLUSIONS

We have discussed the obvious pathol-ogy and, I fear at times, the end point orthe irreversible. However, the lesionswhich are not so obvious should be theones to command our attention.

If we accept the concept of the elec-trical constitution of matter, we cannotescape the conclusion that all change isorganic, and thus it becomes evident thatthe psyche and soma, or the mind andbody, cannot be separated. Differentiationbetween functional and" organic diseaseis purely arbitrary. What is functional to-day will be organic tomorrow when thetechnical advances will allow us to inter-pret the biochemical lesions which up un-til now have not been appreciated.

The diseases which we have discussedhave all been associated with positive eti-ologic factors, at one time or another,such as bacteria, fungi, and viruses. Inthe light of our present knowledge itwould seem more logical to ascribe nega-tive factors as the primary causativeagents in many of than. The lack ofthese substances or the failure to utilizethem, producing disturbances in the en-zyme systems, and thus an unbalancedstate in the organism resulting in whatwe term a morbid state or disease. I

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would like again to emphasize that these"Trophopathic Diseases" are primarilycaused by disturbances of nutrition, and,secondarily, at times by some of theabove positive factors when some of thedefense mechanisms have been inter-fered with.

Let us hope that we arc cognizant ofthe tremendous role that emotions canplay in producing pathology in the or-ganism, but let us not ignore such funda-mental considerations as the part playedby the basic mechanisms that control theirritability and metabolism of the cellitself.

In conclusion, may I reiterate thatwhat you see as dentists, and what we seeas physicians is but part and parcel of thesame morbid processes. We must viewthese trophopathic diseases with a broadunderstanding, bearing in mind, if weare to do the best for our patients, thatwe must consider some of these processesto be less irreversible than has commonlybeen thought in the past. We must ap-proach our work with the optimism thatis warranted by the research advances inthe sciences of which we are a part.

BIBLIOGRAPHY

i. GREEN, D. E.: Advances in Enzymol-ogy, Interscience, New York, 19is, Vol. 1,P. 1 77.

2. BICKNELL, F. and PRESCOTT, F.:The Vitamins in Medicine, :947, p. 352.

3. SPIES, TOM D.: RehabilitationThrough Better Nutrition, 1947.

4. ELLIOTT, H. C.: Textbook of theNervous System, 1947, p.

5. COBB, S.: Foundations of Neuropsy-chiatry, 1948, p. 142.

6. WEIL, A.: Textbook of Neuropathol-ogy, 1945, P. 204.

7. HURST, E. W.: Experimental Dem-yelination of the Central Nervous System, Aus-tralian Journal of Experimental Biology, :942,Vol. 20, pp. 297-312.

8. FOLLIS, R. H.: Pathology of Nutri-tional Disease, 1948, p. 52.

g. FOLLIS, R. H.: Pathology of Nutri-tional Disease, 1948, p. 233.

o. MORRISON, L. R.: DisseminatedEncephalomyelitis Experimentally Produced bythe Use of Homologous Antigen. Archives ofNeurology and Psychiatry, 1947, Vol. 58, pp.391-416.

COBB, S.: Foundations of Neuropsy-chiatry, 1948, p. :76 .

12. CORI, C. F.: Northwestern University,Lecture in Biochemical Chemistry, Dec. 1948.

13. WARKANY, J.: Vitamins and Hor-mones, Edited by Harris, R. S. and Thimann,K. V., 1945, p. 97.

14. SYNDENSTRICKER, V. P.: AnnalsInternal Medicine, 1941, Vol. 15, p. 45•

15. HOPKINS, F. G.: British MedicalJournal, 1923, Vol. 11, p. 693.

16. GREEN, D. E.: Currents in Biochem-ical Research, p. :6o.

17. WOOLEY, D. W.: Science, 1945, Vol.zoo. p. 579.

38. LIPMAN, J. G.: New Jersey Agricul-tural Experiment Station Bulletins, 193o.

13. NORRIS, EARL R. and MAJNAR-ICH, JOHN J.: Action of Enzymes on Vita-min Xi and Pteridines. Science, 1949, Vol.log, pp. 33-35.

so. MITCHELL, H. H.: Journal of Ani-mal Science, 1947, Vol. 6, p. 365.

21. SHELDON, V. L., BLUE, W. G., andALBRECHT, W. A.: Diversity of AminoAcids in Legumes According to the Soil Fer-tility, Science, Vol. :o8, pp. 426-428.

22. COBB, S.: Foundations of Neuropsy-chiatry, 1948, p. 100.

Reprint No. 51

LEE FOUNDATION FOR NUTRITIONAL RESEARCHMilwaukee Wisconsin

Note: Lee Foundation for Nutritional Research Is a non-profit, public-service institution, chartered toinvestigate and disseminate nutritional information. The attached publication is not literature oflabeling for any product, nor shall it be employed as such by anyone. In accordance with the right offreedom of the press guaranteed to the Foundation by the First Amendment of the U.S. Constitution,the attached publication is Issued and distributed for Informational purposes."

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